1.The bridging role of programmed cell death in association between periodontitis and rheumatoid arthritis
GE Ruiyang ; ZHOU Yingying ; MAO Haowei ; HAN Lei ; CUI Di ; YAN Fuhua
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(6):457-465
Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.
2.The mechanism of SAP overexpression in alleviating periodontitis in mice
HUANG Yinyin ; LIANG Dongliang ; ZOU Yaokun ; HAN Jingru ; GE Qing ; LIU Xueyan ; GUO Yadong ; HUANG Xinli ; YANG Lan
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(8):619-630
Objective:
To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis.
Methods:
Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed.
Results:
ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group.
Conclusion
SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.
3.Dexmedetomidine alleviates lung tissue injury of rat models with ventilator-associated lung injury
Huijing HAN ; Hong WU ; Yin GE ; Juan QIAO
Basic & Clinical Medicine 2024;44(3):339-345
Objective To investigate the effect of dexmedetom idine(DEX)on lung tissue and Ras homolog gene family member A(RhoA)/Rho kinase 1(ROCK1)signaling pathway in lung tissue of rats with ventilator-induced lung injury(VILI).Methods A VILI rat model was established and separated into control group,model group(VILI group),dexmedetomidine low and high dose groups(DEX-L,DEX-H group),and high dose dexmedetomi-dine+lysophosphatidic acid(LPA)group(DEX-H+LPA group).Determination of wet/dry mass ratio of rat lung tissue(W/D);HE staining microscopy was applied to observe morphology of lung tissue;ELISA kit was applied to detect the level of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid(BALF);TUNEL staining method was applied to detect lung epithelial cell death;Immunoblotting was applied to detect the expression levels of apoptosis-related proteins,and RhoA,ROCK1 pro-teins.Results DEX could reduce lung injury,lung injury score,W/D,apoptosis rate,levels of TNF-α,IL-1β,IL-6,and expression of Bax,cleaved caspase-3,RhoA,ROCK,α-SMA in VILI rats(P<0.05),while increased the expression of Bcl-2(P<0.05);LPA could aggravate lung injury and increase lung injury score,W/D,apopto-sis rate,level of TNF-α,IL-1β,IL-6 and expressions of Bax,cleaved caspase-3,RhoA,ROCK and α-SMA(P<0.05);Bcl-2 expression level was decreased(P<0.05).Conclusions Dexmedetomidine may protect rats with ventilator-induced lung injury by the inhibition of RhoA/ROCK1 signaling pathway.
4.Research Progress on Factors Affecting the Blood Concentration of Hydroxychloroquine
Xuan HUANG ; Han XIE ; Weihong GE ; Yujie ZHOU
Herald of Medicine 2024;43(2):215-220
Originally used as an antimalarial drug,hydroxychloroquine is now widely used in the treatment of rheumatic immune diseases due to its cost-effectiveness,safety,and efficacy.In addition to its immunomodulatory effects,hydroxychloroquine also exhibits anti thrombotic,anti-hypolipidemic,and anti-hypoglycemic properties.Hydroxychloroquine blood levels are correlated with clinical outcomes and adverse reactions,and can reflect patient compliance.However,due to the complex pharmacokinetic profile of hydroxychloroquine,significant inter-individual differences in blood concentration exist even with the administration of the same dosage.This study investigates the factors affecting the blood concentration of hydroxychloroquine in terms of physiological factors,pathological factors,metabolic enzyme gene polymorphisms,and drug-related factors.The aim is to provide a reference for rational clinical use and the development of individualized dosing.
5.Correction between hand hygiene product consumption and hand hygiene compliance in intensive care units of 74 medical institutions in Shanghai
Hong-Ping PAN ; Meng-Ge HAN ; Qing-Feng SHI ; Bi-Jie HU ; Xiao-Dong GAO
Chinese Journal of Infection Control 2024;23(3):291-297
Objective To understand the consumption of hand hygiene(HH)products and HH compliance in in-tensive care units(ICUs)of secondary and higher grade medical institutions(MIs)in Shanghai,and provide basis for further monitoring of HH among health care workers(HCWs).Methods Through healthcare-associated infec-tion surveillance system,the consumption of HH products and HH compliance in ICUs from secondary and higher grade MIs in Shanghai in 2017-2021 were analyzed.Results 105 ICUs from 74 MIs were included in analysis,the average consumption of HH products was 79.24(44.88-258.63)mL/(bed·day),with statistically significant difference among different types of ICUs(P<0.001).The average consumption of HH products increased from 65.75 mL/(bed·day)in 2017 to 87.55 mL/(bed·day)in 2021,showing an increasing trend year by year(P<0.001).HCWs'HH compliance rate was 82.13%,with the highest in nurses(86.59%)and the lowest(48.90%)in medical technicians,HH compliance rates of HCWs of different occupations were statistically significant different(P<0.001).Among the implementation modes of HH,39.86%used running water for hand washing,42.27%used alcohol-based hand rub to wipe hands,13.22%didn't take HH measures,and 4.65%didn't take HH mea-sures when wearing gloves,with statistically significant differences among different HH implementation modes of HCWs(P<0.001).There was a positive correlation between the average consumption of HH products per bed·day and HCWs'HH compliance rate(r=0.703,P<0.05).Conclusion The average consumption of HH products per bed·day and HH compliance rate of HCWs in ICUs in Shanghai presents an increasing trend year by year.There are differences in the average consumption of HH products per bed·day and HH compliance rate among different types of ICUs.The implementation of HH can be evaluated by continuously surveillance on the average consumption of HH products per bed·day.
6.Innovation and exploration of medical laboratory animal science teaching on the basis of a smart teaching environment
Zihao YANG ; Han MENG ; Zhaonan ZHANG ; Ping ZHANG ; Changhong SHI ; Xu GE
Chinese Journal of Comparative Medicine 2024;34(2):108-113
Objective In the traditional laboratory zoology lecture environment,there is less teacher-student interaction,less student interest,and less engagement in learning.To improve the teaching quality of laboratory animal science,this teaching and research department was based on different teaching environments of multimedia and intelligent classrooms,theoretical course teaching of Medical Laboratory Animal Science as the research object,the course lecture format,teaching mode,teaching method,and other aspects of innovation and exploration.Methods This study used questionnaires to understand changes in student engagement in learning and preferences for smart classroom use,and NVivo qualitative analysis software was used to code student classroom behavior.Results The smart teaching environment resulted in higher student interest and more frequent teacher-student interaction in the classroom.Students were significantly more engaged in learning than in traditional teaching with higher correct rates on in-class and post-lesson exercises and a better grasp of concepts related to laboratory animal science.Conclusions A smart teaching environment brings students a better feeling and experience,improves their interest in laboratory animal science,increases classroom learning engagement,and achieves good teaching result.
7.Correlation between ultrasound parameters of internal carotid artery blood flow and regional cerebral oxygen saturation in elderly patients undergoing coronary artery bypass grafting under CPB
Ying HAN ; Wanlin LI ; Yamei ZHAO ; Haiyan WEI ; Jialin YIN ; Zhonghong SU ; Yali GE ; Hongwei SHI
Chinese Journal of Anesthesiology 2024;44(2):214-219
Objective:To evaluate the correlation between ultrasound parameters of internal carotid artery blood flow and regional cerebral oxygen saturation (rScO 2) in elderly patients undergoing coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Methods:Sixty-four elderly patients undergoing elective CABG under CPB, aged 60-80 yr, regardless of gender, with body mass index of 18.1-28.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, with left ventricular ejection fraction≥50%, were selected. The rScO 2 and ultrasonic parameters of internal carotid artery including peak systolic velocity (PSV-ICA), end-diastolic velocity (EDV-ICA), diameter (D-ICA) and blood flow volume (Q-ICA) were recorded before anesthesia induction (T 0), at surgical skin incision (T 1), at 30 and 60 min of CPB (mean value was calculated, T 2), and at 30 and 60 min after termination of CPB (mean value was calculated, T 3). The ratio of unilateral internal carotid artery blood flow to cardiac output (Q/CO) was calculated. The receiver operating characteristic curve was used to analyze the accuracy of ultrasound parameters of internal carotid artery blood flow in predicting rScO 2 < 60%. Results:PSV-ICA was positively correlated with rScO 2 at T 0, T 1 and T 3 ( P<0.05), but no correlation was found between PSV-ICA and rScO 2 at T 2 ( P>0.05). There was no correlation between EDV-ICA and rScO 2 at each time point ( P>0.05). Q-ICA was positively correlated with rScO 2 at each time point ( P<0.05). Q/CO was not correlated with rScO 2 at T 1 ( P>0.05), but Q/CO was positively correlated with rScO 2 at T 2 and T 3 ( P<0.05). During the non-CPB period (T 0, T 1, T 3), the cutoff values of PSV-ICA and Q-ICA in predicting rScO 2< 60% were 51.35 cm/s and 283.5 ml/min respectively, the sensitivity was 0.900 and 0.900 respectively, and the specificity was 0.610 and 0.857 respectively (AUC=0.761, P=0.006; AUC=0.903, P< 0.001). During the CPB period, the cutoff values of Q-ICA and Q/CO in predicting rScO 2<60% were 296.5 ml/min and 5.84% respectively, the sensitivity was 0.900 and 0.800, and the specificity was 0.545 and 0.659 (AUC=0.764, P=0.001; AUC=0.748, P=0.002), respectively. Conclusions:PSV-ICA and Q-ICA are positively correlated with rScO 2 during the non-CPB period, and Q-ICA and Q/CO are positively correlated with rScO 2 during the CPB period in elderly patients undergoing CABG. PSV-ICA, Q-ICA and Q/CO can accurately predict rScO 2<60%.
8.Clinical effects of Feining Paidu Decoction combined with conventional treatment on patients with Mycoplasma pneumoniae lobar pneumonia
Guo-Cai GAO ; Guo-Lan GE ; Dan-Ping PAN ; Qian-Qian LI ; Xue HAN
Chinese Traditional Patent Medicine 2024;46(1):112-116
AIM To investigate the clinical effects of Feining Paidu Decoction combined with conventional treatment on patients with Mycoplasma pneumoniae lobar pneumonia.METHODS Ninety patients were randomly assigned into control group(45 cases)for 2-week intervention of conventional treatment,and observation group(45 cases)for 2-week intervention of both Feining Paidu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,inflammatory indices(WBC,N,CRP,ESR,PCT),inflammatory cytokines(TNF-α,IL-6,IL-8),coagulation indices(PLT,TT,PT,APTT,Fib,D-D),pulmonary imaging intergal and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,inflammatory indices,inflammatory cytokines,PLT,pulmonary imaging intergal(P<0.05),especially for the observation group(P<0.05);the observation group exhibited prolonged TT,PT,APTT(P<0.05),and decreased Fib,D-D(P<0.05),which were more obvious than those in the control group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with Mycoplasma pneumoniae lobar pneumonia,Feining Paidu Decoction combined with conventional treatment can safely and effectively alleviate clinical symptoms,and improve inflammatory responses,coagulation functions.
9.Ubiquitin-specific protease 42 regulates osteogenic differentiation of human adipose-derived stem cells
Yuan PAN ; Hang GU ; Han XIAO ; Lijun ZHAO ; Yiman TANG ; Wenshu GE
Journal of Peking University(Health Sciences) 2024;56(1):9-16
Objective:To explore the effect of ubiquitin-specific protease 42(USP42)on osteogenic differentiation of human adipose-derived stem cells(hASCs)in vivo and in vitro.Methods:A combina-tion of experiments was carried out with genetic depletion of USP42 using a lentiviral strategy.Alkaline phosphatase(ALP)staining and quantification,alizarin red S(ARS)staining and quantification were used to determine the osteogenic differentiation ability of hASCs under osteogenic induction between the experimental group(knockdown group and overexpression group)and the control group.Quantitative re-verse transcription PCR(qRT-PCR)was used to detect the expression levels of osteogenesis related genes in the experimental group and control group,and Western blotting was used to detect the expression levels of osteogenesis related proteins in the experimental group and control group.Nude mice ectopic im-plantation experiment was used to evaluate the effect of USP42 on the osteogenic differentiation of hASCs in vivo.Results:The mRNA and protein expressions of USP42 in knockdown group were significantly lower than those in control group,and those in overexpression group were significantly higher than those in control group.After 7 days of osteogenic induction,the ALP activity in the knockdown group was sig-nificantly higher than that in the control group,and ALP activity in overexpression group was significantly lower than that in control group.After 14 days of osteogenic induction,ARS staining was significantly deeper in the knockdown group than in the control group,and significantly lighter in overexpression group than in the control group.The results of qRT-PCR showed that the mRNA expression levels of ALP,os-terix(OSX)and collagen type Ⅰ(COL Ⅰ)in the knockdown group were significantly higher than those in the control group after 14 days of osteogenic induction,and those in overexpression group were signifi-cantly lower than those in control group.The results of Western blotting showed that the expression levels of runt-related transcription factor 2(RUNX2),OSX and COL Ⅰ in the knockout group were significant-ly higher than those in the control group at 14 days after osteogenic induction,while the expression levels of RUNX2,OSX and COL Ⅰ in the overexpression group were significantly lower than those in the control group.Hematoxylin-eosin staining of subcutaneous grafts in nude mice showed that the percentage of osteoid area in the knockdown group was significantly higher than that in the control group.Conclusion:Knockdown of USP42 can significantly promote the osteogenic differentiation of hASCs in vitro and in vi-vo,and overexpression of USP42 significantly inhibits in vivo osteogenic differentiation of hASCs,and USP42 can provide a potential therapeutic target for bone tissue engineering.
10.Analysis of therapeutic effect of thalidomide on refractory systemic onset juvenile idiopathic arthritis
Xin CHEN ; Junchen FANG ; Jingxiao GUO ; Lanlan GE ; Fujuan LIU ; Peitong HAN ; Ling LIU
International Journal of Pediatrics 2024;51(2):132-137
Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis(sJIA).Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected,and the clinical manifestations,efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score(sJADAS)was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children(4 males and 6 females)with refractory sJIA,the average age of onset was(7.5±3.3)years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was(4.4±1.7)years,and the longest course of disease was 8.3 years. Before the application of thalidomide,all the 10 children experienced relapses(ranging from 2 to 10 times). The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes[(10.19±3.67)×10 9/L,(8.53±2.83)×10 9/L vs.(16.11±7.81)×10 9/L, F=7.918,11.084, P=0.020,0.009],C-reactive protein[19.13(0.38,35.21)mg/L,8.05(0.10,18.00)mg/L vs. 59.34(24.20,131.90)mg/L, F=7.030,12.731, P=0.026,0.006],sJADAS scores[6.00(1.50,12.50)scores,3.00(0,12.50)scores vs. 20.00(11.50,28.00)scores, F=14.710,17.870, P=0.004,0.002]were decreased significantly. The doses of prednisone[0.13(0,0.45)mg/(kg·d),0.02(0,0.06)mg/(kg·d)vs. 0.42(0.16,1.47)mg/(kg·d), F=5.890,7.623, P=0.041,0.022]were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases,and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA,and can reduce the required dose of prednisone and prolong the tocilizumab free remission.


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